Suo Aleksi, Iqbal Urooj, Lim June, Lee Chel, Gesy Kathy, Iqbal Nayyer, Abbas Tahir
Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Saskatchewan Cancer Agency, Saskatoon, SK, Canada.
Clin Genitourin Cancer. 2017 Jun;15(3):e397-e404. doi: 10.1016/j.clgc.2017.01.016. Epub 2017 Feb 1.
Conventional sunitinib dosing in metastatic renal cell carcinoma (mRCC) administers 50 mg daily on a 4 weeks on/2 weeks off (4/2) schedule. Not all patients tolerate this regimen and many undergo modifications to schedule, dose, or both.
All patients with mRCC treated with sunitinib by the Saskatchewan Cancer Agency between January 1, 2006, and January 1, 2013, were included. Regimens were categorized as standard intermittent dosing (SID), modified intermittent schedule (MIS), modified intermittent dosing (MID), combination of modified schedule and dosing (MSD), or continuous dosing (CD). The primary objective was to compare overall survival (OS) between regimens. Secondary outcomes included progression-free survival (PFS), discontinuation due to adverse effects (AE), and medication cost.
Among 161 patients, 18.0%, 51.6%, and 30.4% had favorable, intermediate, and poor Heng risk prognoses, respectively. A total of 140 (87.0%) received sunitinib as first-line therapy. MID was associated with longer OS compared with SID (estimated median 28.4 vs. 11.2 months). PFS was longer for MID, MSD, and CD compared with SID (estimated median 12.0, 9.0, and 8.0 months vs. 3.0 months, respectively). Adjustment for potential confounders did not negate these associations. SID also had higher average monthly drug costs than MIS, MID, and MSD. Overall discontinuation rate due to AE was high (24%).
An adjusted-dose sunitinib regimen is associated with improved OS and PFS over SID, with lower costs. The development of toxicities requiring dose reductions serves as a predictive biomarker for better outcomes.
转移性肾细胞癌（mRCC）中舒尼替尼的传统给药方案是每日50毫克，采用4周用药/2周停药（4/2）的给药计划。并非所有患者都能耐受该方案，许多患者会对给药计划、剂量或两者进行调整。
纳入2006年1月1日至2013年1月1日期间在萨斯喀彻温癌症机构接受舒尼替尼治疗的所有mRCC患者。治疗方案分为标准间歇给药（SID）、改良间歇给药计划（MIS）、改良间歇给药（MID）、改良给药计划与剂量联合（MSD）或持续给药（CD）。主要目的是比较各治疗方案的总生存期（OS）。次要结局包括无进展生存期（PFS）、因不良反应（AE）停药情况及药物成本。
161例患者中，分别有18.0%、51.6%和30.4%具有良好、中等和不良的恒氏风险预后。共有140例（87.0%）接受舒尼替尼作为一线治疗。与SID相比，MID与更长的OS相关（估计中位生存期分别为28.4个月和11.2个月）。与SID相比，MID、MSD和CD的PFS更长（估计中位生存期分别为12.0、9.0和8.0个月，而SID为3.0个月）。对潜在混杂因素进行调整并未消除这些关联。SID的平均每月药物成本也高于MIS、MID和MSD。因AE导致的总体停药率较高（24%）。
调整剂量的舒尼替尼方案与SID相比，OS和PFS得到改善，且成本更低。因毒性反应需要降低剂量可作为预后较好的预测生物标志物。
